This application requests support for the Center for Inherited Diseases - an interdisciplinary Center at the University of Washington dealing with various aspects of medical genetics. The Center brings together investigators interested in both basic and applied human genetics. Its principal aim is better understanding and ultimately better treatment and prevention of human hereditary diseases. Core units supply the necessary biochemical, cytogenetic, computer-statistical, and clinical skills and resources for optimal investigations. The Center carries out a variety of studies in human and medical genetics with particular reference to common diseases including the study of the molecular genetics of lipoproteins in susceptibility to coronary heart disease, identification of specific genes involved in membrane transport in hypertension, possible molecular collagen abnormalities in osteoporosis, and biochemical genetic study of genetic variation of paraoxonase in determining different susceptibility to insecticide poisoning. Attempts will be made to identify the gene and gene products of cystic fibrosis using new molecular techniques. The developmental switch from alpha-fetoprotein to albumin production will be investigated in order to identify specific regulatory genes affecting development. Homologous areas on the X and Y chromosome will be studied in order to better understand the mechanisms by which X and Y chromosomal action is regulated. The specific contribution of oncogenes to neoplasia will be explored in experimental skin tumor initiation and progression.